Developing red thermally activated delayed fluorescence (TADF) emitters, attainable for both high‐efficient red organic light‐emitting diodes (OLEDs) and non‐doped deep red/near‐infrared (NIR) OLEDs, ...is challenging. Now, two red emitters, BPPZ‐PXZ and mDPBPZ‐PXZ, with twisted donor–acceptor structures were designed and synthesized to study molecular design strategies of high‐efficiency red TADF emitters. BPPZ‐PXZ employs the strictest molecular restrictions to suppress energy loss and realizes red emission with a photoluminescence quantum yield (ΦPL) of 100±0.8 % and external quantum efficiency (EQE) of 25.2 % in a doped OLED. Its non‐doped OLED has an EQE of 2.5 % owing to unavoidable intermolecular π–π interactions. mDPBPZ‐PXZ releases two pyridine substituents from its fused acceptor moiety. Although mDPBPZ‐PXZ realizes a lower EQE of 21.7 % in the doped OLED, its non‐doped device shows a superior EQE of 5.2 % with a deep red/NIR emission at peak of 680 nm.
Two red emitters, BPPZ‐PXZ and mDPBPZ‐PXZ, with twisted donor–acceptor structures were designed and synthesized to study molecular design strategies of high‐efficiency red TADF emitters. BPPZ‐PXZ employs the strictest molecular restrictions to suppress energy loss and realizes red emission with a photoluminescence quantum yield (ΦPL) of 100±0.8 % and external quantum efficiency (EQE) of 25.2 % in a doped OLED.
Synapses, the fundamental unit in neuronal circuits, are critical for learning and memory, perception, thinking, and reaction. The neuromuscular junction (NMJ) is a synapse formed between motoneurons ...and skeletal muscle fibers that is covered by Schwann cells (SCs). It is essential for controlling muscle contraction. NMJ formation requires intimate interactions among motoneurons, muscles, and SCs. Deficits in NMJ formation and maintenance cause neuromuscular disorders, including congenital myasthenic syndrome and myasthenia gravis. NMJ decline occurs in aged animals and may appear before clinical presentation of motoneuron disorders such as amyotrophic lateral sclerosis. We review recent findings in NMJ formation, maintenance, neuromuscular disorders, and aging of the NMJ, focusing on communications among motoneurons, muscles and SCs, and underlying mechanisms.
Neural tissue requires a great metabolic demand despite negligible intrinsic energy stores. As a result, the central nervous system (CNS) depends upon a continuous influx of metabolic substrates from ...the blood. Disruption of this process can lead to impairment of neurological functions, loss of consciousness, and coma within minutes. Intricate neurovascular networks permit both spatially and temporally appropriate metabolic substrate delivery. Lactate is the end product of anaerobic or aerobic glycolysis, converted from pyruvate by lactate dehydrogenase-5 (LDH-5). Although abundant in the brain, it was traditionally considered a byproduct or waste of glycolysis. However, recent evidence indicates lactate may be an important energy source as well as a metabolic signaling molecule for the brain and astrocytes—the most abundant glial cell—playing a crucial role in energy delivery, storage, production, and utilization. The astrocyte–neuron lactate-shuttle hypothesis states that lactate, once released into the extracellular space by astrocytes, can be up-taken and metabolized by neurons. This review focuses on this hypothesis, highlighting lactate’s emerging role in the brain, with particular emphasis on its role during development, synaptic plasticity, angiogenesis, and disease.
Schizophrenia is a highly debilitating mental disorder that affects approximately 1% of the general population, yet it continues to be poorly understood. Recent studies have identified variations in ...several genes that are associated with this disorder in diverse populations, including those that encode neuregulin 1 (NRG1) and its receptor ErbB4. The past few years have witnessed exciting progress in our knowledge of NRG1 and ErbB4 functions and the biological basis of the increased risk for schizophrenia that is potentially conferred by polymorphisms in the two genes. An improved understanding of the mechanisms by which altered function of NRG1 and ErbB4 contributes to schizophrenia might eventually lead to the development of more effective therapeutics.
Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders with symptoms including social deficits, anxiety, and communication difficulties. However, ASD pathogenic mechanisms are ...poorly understood. Mutations of CUL3, which encodes Cullin 3 (CUL3), a component of an E3 ligase complex, are thought of as risk factors for ASD and schizophrenia (SCZ). CUL3 is abundant in the brain, yet little is known of its function. Here, we show that CUL3 is critical for neurodevelopment. CUL3-deficient mice exhibited social deficits and anxiety-like behaviors with enhanced glutamatergic transmission and neuronal excitability. Proteomic analysis revealed eIF4G1, a protein for Cap-dependent translation, as a potential target of CUL3. ASD-associated cellular and behavioral deficits could be rescued by pharmacological inhibition of the eIF4G1 function and chemogenetic inhibition of neuronal activity. Thus, CUL3 is critical to neural development, neurotransmission, and excitation-inhibition (E-I) balance. Our study provides novel insight into the pathophysiological mechanisms of ASD and SCZ.
•Cul3 mutant mice exhibits social behavioral deficits and anxiety-like behaviors•CUL3 deficiency impairs neurotransmission, excitability, and E-I balance•Protein translation and synaptic vesicle turnover are increased in Cul3 mutant mice•Inhibiting protein translation rescues social behavior and neurotransmission deficits
Mutations of CUL3, a component of an E3 ligase complex, are thought of as risk factors for autism spectrum disorders (ASDs) and schizophrenia. Here, Dong et al. show CUL3 deficiency in mice causes social deficits and anxiety-like behaviors and enhances glutamatergic transmission and neuronal excitability. Proteomic analysis reveals eIF4G1, a protein for Cap-dependent translation, as a potential target of CUL3 deficiency. Pharmacological inhibition of eIF4G1 and chemogenetic inhibition of neuronal activity attenuates ASD-associated cellular and behavioral deficits.
The dentate gyrus, a “gate” that controls the flow of information into the hippocampus, is critical for learning, memory, spatial navigation, and mood regulation. Several lines of evidence have ...demonstrated that deficits in dentate granule cells (DGCs) (e.g., loss of DGCs or genetic mutations in DGCs) contribute to the development of various psychiatric disorders, such as depression and anxiety disorders. Whereas ventral DGCs are believed to be critical for mood regulation, the functions of dorsal DGCs in this regard remain elusive. Here, we review the role of DGCs, in particular the dorsal DGCs, in the regulation of mood, their functional relationships with DGC development, and the contributions of dysfunctional DGCs to mental disorders.
Formation of a single‐component charge‐transfer complex (SCCTC) is unveiled in solid state of an intermolecular charge‐transfer molecule ...2‐(4‐(1‐phenyl‐1H‐phenanthro9,10‐dimidazol‐2‐yl)phenyl)anthracene‐9,10‐dione (PIPAQ). Intermolecular donor–acceptor interactions between two PIPAQ molecules is the primary driving force for self‐association and contributes to intermolecular charge transfer. The SCCTC character is fully verified by crystallographic, photophysical, electron spin resonance, and vibrational characterizations. The PIPAQ‐based SCCTC is first applied in light‐emitting devices as an emissive layer to realize efficient deep‐red/near‐infrared electroluminescence. This work provides new insights into SCCTC and represents an important step toward their applications in optoelectronic devices.
Dimeric single‐component charge‐transfer complexes (SCCTCs) by self‐complexation of a donor–π–acceptor molecule (PIPAQ) are revealed and fully investigated, wherein the strong intermolecular charge transfer leads to unprecedented deep‐red/near‐infrared emission. The SCCTCs can be formed in thin films and applied in electroluminescence devices to realize high efficiencies via a thermally activated delayed fluorescence channel.
To determine if patients with myasthenia gravis (MG) have antibodies to agrin, a proteoglycan released by motor neurons and is critical for neuromuscular junction (NMJ) formation, we collected serum ...samples from 93 patients with MG with known status of antibodies to acetylcholine receptor (AChR), muscle specific kinase (MuSK) and lipoprotein-related 4 (LRP4) and samples from control subjects (healthy individuals and individuals with other diseases). Sera were assayed for antibodies to agrin. We found antibodies to agrin in 7 serum samples of MG patients. None of the 25 healthy controls and none of the 55 control neurological patients had agrin antibodies. Two of the four triple negative MG patients (i.e., no detectable AChR, MuSK or LRP4 antibodies, AChR-/MuSK-/LRP4-) had antibodies against agrin. In addition, agrin antibodies were detected in 5 out of 83 AChR+/MuSK-/LRP4- patients but were not found in the 6 patients with MuSK antibodies (AChR-/MuSK+/LRP4-). Sera from MG patients with agrin antibodies were able to recognize recombinant agrin in conditioned media and in transfected HEK293 cells. These sera also inhibited the agrin-induced MuSK phosphorylation and AChR clustering in muscle cells. Together, these observations indicate that agrin is another autoantigen in patients with MG and agrin autoantibodies may be pathogenic through inhibition of agrin/LRP4/MuSK signaling at the NMJ.
The neuromuscular junction (NMJ) is a tripartite synapse that is formed by motor nerve terminals, postjunctional muscle membranes, and terminal Schwann cells (TSCs) that cover the nerve-muscle ...contact. NMJ formation requires intimate communications among the three different components. Unlike nerve-muscle interaction, which has been well characterized, less is known about the role of SCs in NMJ formation and maintenance. We show that SCs in mice lead nerve terminals to prepatterned AChRs. Ablating SCs at E8.5 (i.e., prior nerve arrival at the clusters) had little effect on aneural AChR clusters at E13.5, suggesting that SCs may not be necessary for aneural clusters. SC ablation at E12.5, a time when phrenic nerves approach muscle fibers, resulted in smaller and fewer nerve-induced AChR clusters; however, SC ablation at E15.5 reduced AChR cluster size but had no effect on cluster density, suggesting that SCs are involved in AChR cluster maturation. Miniature endplate potential amplitude, but not frequency, was reduced when SCs were ablated at E15.5, suggesting that postsynaptic alterations may occur ahead of presynaptic deficits. Finally, ablation of SCs at P30, after NMJ maturation, led to NMJ fragmentation and neuromuscular transmission deficits. Miniature endplate potential amplitude was reduced 3 d after SC ablation, but both amplitude and frequency were reduced 6 d after. Together, these results indicate that SCs are not only required for NMJ formation, but also necessary for its maintenance; and postsynaptic function and structure appeared to be more sensitive to SC ablation.
Neuromuscular junctions (NMJs) are critical for survival and daily functioning. Defects in NMJ formation during development or maintenance in adulthood result in debilitating neuromuscular disorders. The role of Schwann cells (SCs) in NMJ formation and maintenance was not well understood. We genetically ablated SCs during development and after NMJ formation to investigate the consequences of the ablation. This study reveals a critical role of SCs in NMJ formation as well as maintenance.
PDF
